The proposal is to study the activity of the enzymes of glycogen metabolism in states of insulin resistance caused either by insulin deficiency in dog, rat or human (or by growth hormone administration - dog only). Observations to date have shown that one possible cause of insulin resistance (in insulin deficiency) is a failure of glycogen synthetase D phosphatase in liver to become activated with insulin whereas, in these same pancreatectomized dogs, maintained with daily insulin, the same infusions of insulin and glucose result in an increase over control activity of the phosphatase. Therefore, purification and characterization of this enzyme is planned, making use of information gained this past year from partial purification of phospho-histone and phosphatase of liver and from a previous study of the phosphatases of skeletal muscle. Another aspect of the proposal is to study the glycogen enzymes of circulating leukocytes to determine whether changes in these cells during states of insulin resistance resemble the changes in liver.